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Biomedical subjects

N Berkman

Publications and source records attributed to N Berkman.

At least 37 records · Page 2Linked to original sources
PubMed1997

Bleomycin-induced lung injury is enhanced by interferon-alpha.

We have evaluated the effect of intraperitoneal (I.P.) injection of human recombinant interferon-2alpha (IFN-alpha) on Bleomycin-induced pulmonary injury in hamsters. Pulmonary injury was induced by a single intratracheal (I.T.) instillation of Bleomycin (Bleo). Six groups of male Syrian hamsters were treated as follows: 1) I.T. Bleo and daily I.P. injections of low-dose interferon-alpha (2 x 10(4) U), 2) I.T. Bleo and daily I.P. injections of high-dose interferon-alpha (10(5) U), 3) I.T. Bleo and I.P. injections of saline, 4) I.T. saline and I.P. low-dose IFN-alpha, 5) I.T. saline and I.P. high-dose IFN-alpha, 6) I.T. saline and I.P. saline. Animals were sacrificed 28 days after I.T. treatment. Lung injury was evaluated histologically and biochemically. Treatment of hamsters with low-dose but not high-dose IFN-alpha significantly augmented the Bleo-induced lung injury, as determined by a semiquantitative morphological index. Lung hydroxyproline measurements were highest in Bleo-low-dose-IFN-alpha followed by Bleo-high-dose-IFN-alpha and Bleo-Sal as compared to Sal-Sal and Sal-IFN-alpha controls. These results suggest that IFN-alpha augments Bleo-induced lung injury but that this effect is complex and does not follow a simple-dose-response pattern.

Animals↗
PubMed1997

Primary non-Hodgkin's lymphoma of the lung presenting as bronchiolitis obliterans organizing pneumonia.

A 44-year-old man presented with fever, dyspnea, and bilateral cavitary lung lesions. Following percutaneous transthoracic CT guided needle biopsy of the lung, a diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP) was made and the patient was treated with corticosteroids. Despite a good initial response he developed new lung lesions within six months, associated with a lack of response to corticosteroids. Due to further deterioration and the development of Guillian-Barre' syndrome an open lung biopsy was performed and revealed T-cell rich, B-cell non Hodgkin's lymphoma with BOOP. We suggest that BOOP may be the presenting manifestation of primary lung lymphoma. We recommend that when BOOP has an atypical course or does not respond to corticosteroids open lung biopsy should be performed in order to exclude pulmonary lymphoma.

Adult↗
PubMed1997

Clustering of Pneumocystis carinii pneumonia in patients undergoing renal transplantation from living unrelated donors in Iraq and India.

Over the past few years, we have observed a substantial increase in the number of patients followed at our hospital who have undergone renal transplantation from living unrelated donors (LURD). These transplants were all performed in one of two centers: Bagdad, Iraq or Bombay, India. We have observed a parallel increase in the number of cases of Pneumocystis carinii pneumonia (PCP) post-renal transplant. We conducted a ten-year retrospective analysis (1986-1995) of patients who developed PCP post-renal transplant to determine the risk factors associated with the development of this infection, with particular reference to the type of transplant and the center in which the transplant was performed. Over this period, 270 renal transplant patients were followed at this hospital and 10 episodes of PCP were documented (3.7%). Six of these cases occurred within the last 2 years, as compared to only 4 cases in the preceding 8 years. All of the cases observed in the last 2 years occurred in patients who had undergone renal transplantation from LURD in Iraq or in India. During the same period, we observed no cases of PCP in patients who had undergone transplantation in Israel (cadaver or related living donor transplants). We could find no difference between patients undergoing transplant from LURD and those undergoing other transplants in terms of immuno-suppressive therapy, frequency of organ rejection episodes or coexistent CMV infection. All patients were of Arab descent and live in the West Bank. Although we cannot identify any obvious explanation for this association, we believe that these cases represent a true cluster phenomenon. We therefore feel it is warranted for all recipients of renal transplants from living unrelated donors seen in our hospital to receive prophylactic therapy for Pneumocystis carinii pneumonia.

Adult↗
PubMed1996

Expression of RANTES in human airway epithelial cells: effect of corticosteroids and interleukin-4, -10 and -13.

RANTES is a C-C chemokine with strong chemoattractant and activating properties for eosinophils, basophils and T lymphocytes. We investigated the expression of RANTES in human airway epithelial cells and its modulation. Epithelial cells obtained from tracheas of donor lungs were stimulated with interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) or with a mixture of the three cytokines ('cytomix'). Levels of mRNA and protein were assayed by Northern blot and radioimmunoassay, respectively. Each individual cytokine produced a small increase in RANTES protein: IL-1 beta 24 +/- 1 pM, TNF-alpha 13 +/- 7 pM and IFN-gamma 29 +/- 7 pM, but cytomix increased protein to 236 +/- 22 pM (P < 0.002) and mRNA expression by > 20-fold (P < 0.002). Both RANTES protein and mRNA expression were inhibited by dexamethasone (10(-6) M) (38 +/- 5%, P < 0.05 and 55 +/- 8%, P < 0.007, respectively), and by IL-4 (42 +/- 7%, P < 0.03 and 19 +/- 1%, not significant, respectively). No inhibitory effect was observed with IL-10 or IL-13. We also demonstrated in vivo expression of RANTES protein by epithelial cells in human airways using immunohistochemistry. Our data show that human airway epithelial cells can be stimulated to express and release RANTES, an effect that is inhibited by corticosteroids and IL-4, but not by IL-10 and IL-13.

Blotting, Northern↗
PubMed1996

Inhibition of inducible nitric oxide synthase expression by interleukin-4 and interleukin-13 in human lung epithelial cells.

Nitric oxide produced by the inducible enzyme, nitric oxide synthase (iNOS), is implicated in immunological and inflammatory processes. We determined the effects of T-helper (Th)2-derived cytokines on the induction of iNOS from an epithelial A549 cell line and human airway epithelial cells stimulated by a mixture of interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). Interleukin-4 (IL-4) and interleukin-13 (IL-13) but not interleukin-10 (IL-10) inhibited both iNOS mRNA expression and nitrite release in A549 cells. On human airway epithelial cells, IL-4 and IL-13 reduced iNOS mRNA expression. Dexamethasone also inhibited both iNOS expression and nitrite release. Th2 cytokines, IL-4 and IL-13, inhibit iNOS upregulation by Th1 cytokines, indicating an important reciprocal role of Th1 and Th2 T-cell subsets on lung epithelial cells.

Blotting, Northern↗
PubMed1996

Pyelonephritis as a cause of pleural effusion.

Although pancreatitis and subphrenic abscess frequently cause pleural effusion, renal disease rarely does so. We report a case of a young patient who presented with pleural effusion due to pyelonephritis and renal outflow obstruction secondary to nephrolithiasis. The effusion and the initial absence of urinary abnormalities resulted in delay in diagnosis and initiation of appropriate therapy.

Adult↗
PubMed1996

Expression of RANTES mRNA and protein in airways of patients with mild asthma.

Chemoattractant cytokines (chemokines) such as RANTES, are potent chemoattractants for eosinophils, T lymphocytes, and monocyte/macrophages. We examined RANTES mRNA and protein expression in bronchial biopsies and bronchoalveolar lavage (BAL) cells from patients with mild asthma on beta 2-adrenergic agonist therapy only. Using quantitative polymerase chain reaction (PCR), mean RANTES starting cDNA was 110 +/- 18 fg/pg beta-actin in asthmatics compared with 33.7 +/- 11.0 fg/pg in normals (p < 0.003) but there was no significant difference in RANTES mRNA expression in BAL cells between the two groups. Immunohistochemical staining of cryostat sections of bronchial biopsies with an anti-RANTES antibody using peroxidase antiperoxidase method revealed constitutive staining in airway epithelial cells, airway smooth muscle, and subepithelial cells. However, there was no difference in the number of RANTES-staining cells between normal subjects and asthmatics despite significantly increased numbers of CD4+ T-cells, CD68+ macrophages, and MBP+ eosinophils in mucosal biopsies obtained from asthmatics. Double-staining revealed expression of RANTES in a proportion of CD3+ T lymphocytes. Thus, RANTES is constitutively expressed in the airways and RANTES mRNA is elevated in airways of patients with mild asthma, supporting a role for RANTES in normal and asthmatic airways.

Actins↗
PubMed1996

Interleukin 13 inhibits macrophage inflammatory protein-1 alpha production from human alveolar macrophages and monocytes.

Interleukin 13 (IL-13) is a recently described protein secreted by activated T cells and is a potent in vitro modulator of human monocyte and B-cell functions. IL-13 shares some biologic properties as well as structural similarities with IL-4. Macrophage-inflammatory protein 1 alpha (MIP-1 alpha) is a product of activated monocytes and macrophages and an important activator of T cells, monocytes, and macrophages. We determined the effect of human recombinant IL-13 on lipopolysaccharide (LPS)- and IL-1 beta-induced MIP-1 alpha mRNA and protein expression from peripheral blood monocytes (PBM) and alveolar macrophages (AM). In PBM, basal MIP-1 alpha protein was 20 +/- 7 pM and increased following LPS and IL-1 beta to 1,520 +/- 193 (P < 0.001) and 233 +/- 50 (P < 0.003) pM. IL-13 (25 ng/ml) reduced these values by 55 +/- 10% [not significant (NS)], 43 +/- 9% (P < 0.03), and 44 +/- 15% (NS), respectively. LPS- and IL-1 beta-induced MIP-1 alpha mRNA expression was reduced by 43 +/- 5% (P < 0.01) and 41 +/- 4% (NS). In AM, IL-13 reduced LPS-induced MIP-1 alpha protein release of 2,030 +/- 242 pM by 32 +/- 8% (P < 0.05) and MIP-1 alpha mRNA by 27 +/- 1% (NS). For both PBM and AM, the inhibitory effect of IL-13 on MIP-1 alpha protein was maximal at 24 h, was dose dependent with a maximal effect at 100 ng/ml, and was similar to, although slightly less potent than, that seen with IL-4. In PBM, the inhibitory effect of IL-13 required de novo protein synthesis and was not due to enhanced mRNA decay. Thus, IL-13 has inhibitory effects on the transcription of MIP-1 alpha from monocytes and macrophages, and as is the case with IL-4 and IL-10, may be an important mediator for suppressing inflammatory responses.

Blotting, Northern↗
PubMed1996

Pulmonary involvement in lymphoma.

Intrathoracic involvement is common in both Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). The most common manifestation is mediastinal lymphadenopathy. In HD, nodal involvement is by contiguity and usually involves the superior mediastinum, while the findings in NHL are more variable. Pulmonary parenchymal disease occurs in 38% of HD and 24% of NHL. In untreated HD, parenchymal involvement is invariably associated with mediastinal lymphadenopathy and often with widespread disease. Three distinct radiological patterns of pulmonary lymphoma are recognised: nodular, bronchovascular-lymphangitic and pneumonic-alveolar. Rarely lymphoma may be endobronchial. Pleural effusion occurs in 16% of lymphoma patients and is usually associated with disease elsewhere. It is frequently caused by lymphatic obstruction but may be due to direct pleural involvement by tumour. Chylothorax may occur in NHL but is unusual in HD. Diagnosis of intrathoracic lymphoma is by transbronchial or transthoracic biopsy or by needle aspiration of tissue or pleural fluid. The addition of immunostaining improves the diagnostic yield in equivocal cases. Treatment and prognosis vary depending on cell-type, location and extent of disease.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Inhibition of macrophage inflammatory protein-1 alpha expression by IL-10. Differential sensitivities in human blood monocytes and alveolar macrophages.

IL-10 is a pleiotropic cytokine produced by monocytes and T cells that has potent inhibitory effects on monocyte/macrophage function. Because monocytes and macrophages are capable of releasing the C-C chemokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha), which is a potent chemoattractant for activated T cells, we studied the effects of IL-10 on the expression of MIP-1 alpha in these cells. Low levels of MIP-1 alpha were detectable in resting monocytes and macrophages. Both LPS (1 micrograms/ml) and IL-1 beta (10 ng/ml) induced the expression of MIP-1 alpha mRNA and the release of MIP-1 alpha protein from these cells. The addition of exogenous human rIL-10 inhibited induced MIP-1 alpha mRNA expression as well as the release of MIP-1 alpha protein measured after 24 h. This inhibition was significantly higher in monocytes compared with alveolar macrophages. In monocytes, IL-10-induced inhibition of MIP-1 alpha was only partially accounted for by alterations in mRNA stability and was dependent on de novo protein synthesis. In the presence of an anti-human IL-10-neutralizing Ab, the release of MIP-1 alpha induced by LPS and IL-1 beta was further enhanced in monocytes but unchanged in alveolar macrophages. MIP-1 alpha mRNA was also increased in monocytes. There was no detectable release of IL-10 from alveolar macrophages after LPS or IL-1 beta in contrast to modest amounts released from monocytes. Thus, IL-10 is an inhibitor of the induced transcription of MIP-1 alpha mRNA and of the release of MIP-1 alpha protein, with a greater effect on monocytes as compared with alveolar macrophages. IL-10 may indirectly regulate effects on cells such as activated T lymphocytes partly through the inhibition of MIP-1 alpha expression from monocytes and macrophages.

Antibodies↗
PubMed1995

Corticosteroid inhibition of macrophage inflammatory protein-1 alpha in human monocytes and alveolar macrophages.

One of the major inducible cytokines secreted by mononuclear phagocytes is macrophage inflammatory protein 1 (MIP-1), which consists of two homologous polypeptides, MIP-1 alpha and MIP-1 beta. MIP-1 alpha possesses chemotactic and stimulatory activities for lymphocytes, eosinophils, and monocytes and may play a role in various pulmonary inflammatory conditions. We investigated the expression and release of MIP-1 alpha from human peripheral blood monocytes (PBM) and alveolar macrophages (AM) after stimulation with lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha, and interferon-gamma and the inhibitory effects of corticosteroids. LPS and IL-1 beta only enhanced MIP-1 alpha mRNA and protein in a dose- and time-dependent fashion. Dexamethasone (10(-9) to 10(-4) M) inhibited the basal and induced production and expression of MIP-1 alpha. In PBM, dexamethasone (10(-6) M) reduced LPS- and IL-1 beta-stimulated production of MIP-1 alpha protein by 50 and 63%, respectively, maximally at 24 h, whereas the inhibition of mRNA expression occurred maximally at 4 h. Similar trends were observed for AM. MIP-1 alpha mRNA decay was only slightly decreased in the presence of dexamethasone. Inhibition of LPS-induced MIP-1 alpha mRNA by dexamethasone was attenuated by the protein synthesis inhibitor cycloheximide, indicating the involvement of a protein intermediate. Corticosteroids are a potent inhibitor of IL-1 beta- and LPS-induced expression of MIP-1 alpha through mechanisms involving mainly inhibition of transcription and to a minor degree by reducing mRNA stability. Corticosteroids may be effective anti-inflammatory agents by preventing the expression of chemokines such as MIP-1 alpha.

Base Sequence↗
PubMed1994

Eotaxin: cloning of an eosinophil chemoattractant cytokine and increased mRNA expression in allergen-challenged guinea-pig lungs.

Eotaxin was recently identified as the major eosinophil chemoattractant in bronchoalveolar lavage fluid obtained 3h after allergen challenge of sensitised guinea-pigs. We now report the cDNA cloning of this C-C chemokine. The 777 base-pair clone, pEo3122, consists of a 40 base 5' untranslated region, an open reading frame of 288 bases predicting a 73 amino acid mature protein plus a 23 amino acid signal peptide, and a 3' untranslated region of 449 bases containing a poly A tail. Northern blot analysis showed eotaxin mRNA in the lungs of naive and sensitised guinea-pigs, which was considerably increased after allergen challenge. Eotaxin may be an important mediator of eosinophil accumulation and activation in allergic reactions. As eotaxin stimulates human eosinophils, this chemokine and related molecules may be involved in human diseases such as asthma where eosinophil accumulation is a prominent feature.

Allergens↗
PubMed1994

Effect of natural oxygen enrichment at low altitude on oxygen-dependent patients with end-stage lung disease.

OBJECTIVE: To assess the effect of lowering altitude to that of the lowest place on earth (Dead Sea) on arterial oxygenation and exercise performance in patients with hypoxemia and end-stage lung disease. DESIGN: A cohort of 10 patients. SETTING: Pulmonary function laboratories in Jerusalem, Israel, and at the Dead Sea. PATIENTS: 10 patients with end-stage lung disease who were receiving long-term oxygen therapy. The 4 males and 6 females were 12 to 77 years old. Four patients had chronic obstructive pulmonary disease; 2 had cystic fibrosis; 3 had pulmonary fibrosis; and 1 had pulmonary hypertension (thromboembolic). Mean forced vital capacity was 1.54 L (54% of predicted value) and mean forced expiratory volume in 1 second was 0.85 L (35% of predicted value). MEASUREMENTS: Spirometry, blood gas analysis, progressive exercise testing, and sleep oximetry were done in Jerusalem (altitude, 800 m above sea level; barometric pressure, 696 mm Hg); the same measurements were done 6 days after arrival at the Dead Sea (altitude, 402 m below sea level; barometric pressure, 800 mm Hg) and then 7 to 14 days later in Jerusalem. RESULTS: Arterial oxygenation increased from a median partial pressure of arterial oxygen of 51.6 mm Hg in Jerusalem to 67.0 mm Hg at the Dead Sea, an increase of 15.2 mm Hg (95% CI of paired difference, 4.1 to 20.4 mm Hg; P = 0.001). Partial pressure of arterial carbon dioxide increased from a median of 43.2 to 45.9 mm Hg, an increase of 2.7 mm Hg (CI, 0.5 to 6.4 mm Hg; P = 0.004), with a borderline significant change in the alveolar-arterial gradient. Arterial oxygen saturation increased from a median of 87.7% to 92.8%, a change of 4.8% (CI, 1.9% to 9.8%; P = 0.003). Exercise performance also improved as maximum oxygen uptake increased from a median of 827 mL/min to 1056 mL/min, an increase of 203 mL/min (CI, 54 to 388 mL/min; P = 0.006). Sleep oximetry also improved as median arterial oxygen saturation measured during sleep increased from 85% to 90%, a change of 5% (CI, 2% to 7%; P = 0.005), and percentage of sleep time with an oxygen saturation rate of 90% or more increased from a median of 24% to 73%, a change of 49% (CI, 20% to 87%; P = 0.02). No change in spirometry was noted. All patients felt less dyspneic and reported improved functional capacity with reduced need for oxygen. CONCLUSION: Descent to low altitude can improve arterial oxygenation, exercise performance, and sleep oximetry and consequently the quality of life in patients with hypoxemia and advanced lung disease.

Adolescent↗
PubMed1994

Pharmacokinetic analysis of two new sustained-release products of diltiazem designed for twice- and once-daily treatment.

The pharmacokinetics of two new sustained-release (SR) products of diltiazem, Dilapress 120 mg tablets and Dilapress 240 mg tablets, was analysed and characterized in three different studies, in comparison to the following diltiazem SR formulations: Cardizem Retard, Cardizem SR, and Cardizem CD. Dilapress 120, designated for twice-daily dosing, was found to be bioequivalent to Cardizem SR and to Cardizem Retard with mean (+/- SD) relative bioavailability values of 99 +/- 27% and 113 +/- 38%, respectively. Dilapress 240, designed for once-a-day treatment, was found to have a slower absorption rate than Cardizem SR and its extent of absorption was 56 +/- 19% relative to that of Cardizem SR. However, the bioavailability of Dilapress 240 relative to that of Cardizem CD was 118 +/- 46%, indicating that the bioavailability of Cardizem CD relative to that of Cardizem SR was only 54 +/- 29%. Diltiazem is partially available due to a saturable liver first-pass effect. A high dose of Cardizem SR may partially escape this first-pass effect and, thus, achieve a higher extent of absorption than a slower SR product. Consequently, SR products of diltiazem designed for once-daily treatment may not reach the saturation stage in the liver first-pass effect process that diltiazem is susceptible to. Consequently, a twice-daily SR product of diltiazem cannot serve as a reference for extent of absorption assessments of a once-daily SR product.

Absorption↗